Hormonal and acoustic regulation of the dopaminergic auditory efferent system: improving detection of social acoustic signals at the level of the inner ear - While there is ample evidence that the dopaminergic inner ear efferent system is upregulated under environmental conditions that induce acoustic trauma, there is a major gap in knowledge about internal regulators of this system and its functional significance under normal hearing conditions, especially in the context of social communication. The overall objective of this application is to determine the hormonal and acoustic signals that underlie the plasticity of dopamine innervation and its synthesis in the inner ear, which, in turn, affects primary auditory processing and encoding of social vocalizations. The plainfin midshipman fish, perhaps the most robust model for this kind of work has the enormous potential of uncovering regulation and function of dopaminergic inner ear efferents in the context of social communication. Importantly, the natural and extraordinary plasticity of the peripheral auditory system (including its dopaminergic efferents) in female midshipman, appears to mirror conditions reflective of human hearing loss and attention. The central hypothesis is that the dopaminergic system of the inner ear is regulated by changes in internal state via circulating hormones and local synthesis of dopamine can be modulated by social acoustic stimuli. This hypothesis, strongly supported by preliminary data, will be tested by the following two specifc aims: 1) Measure hormone-induced changes in dopaminergic neurotransmission and 2) Characterize changes in dopamine synthesis and metabolism after exposure to social acoustic signals. For the first aim circulating levels of sex steroids and melatonin will be experimentally manipulated and changes in dopamine innervation, dopamine receptor gene expression and dopamine synthesis and metabolism in the inner ear will be measured. For the second aim, changes in local dopamine synthesis in the inner ear of females will be measured when exposed to male advertisement calls and when responding and attending to social acoustic stimuli. The proposed project is innovative, in our opinion, because it represents a substantive departure from the status quo by employing a simple but powerful, non-mammalian vertebrate model system where hormone-driven increases in periphery auditory sensitivity enhance encoding of social acoustic signals, and dopamine input to the inner ear plays a role in mediating this change in auditory sensitivity. This contribution will be significant because it will identify physiological and environmental conditions that regulate a novel biological function for dopamine in the peripheral auditory system: increased detection of social-acoustic signals. Importantly, our results could interpret the function of dopamine modulation of the inner ear in a natural and behaviorally relevant context that is absent in mammalian studies thus far. Ultimately, these findings have the potential to provide insights into how cycling (menstrual) or decline in hormones (aging) may be linked to changes in hearing sensitivity and attention as well as brain diseases such as ASD and ADHD where orientation to and detection of social auditory cues is severely impaired.
